Ultra-Sensitive Step-Function Opsin for Deep Brain Stimulation
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Solution Overview
Problem
Current optogenetic methods for neurological disease treatment are invasive, causing tissue damage and limited anatomical coverage due to light attenuation in brain tissues, increasing susceptibility to infection and failing to effectively target deep brain regions.
Innovation Solution
Development of ultra-sensitive step-function opsin (SOUL) compositions and methods for minimally invasive optogenetic stimulation using external optical activation, allowing for transcranial or transdural stimulation without surgical implants, enabling modulation of neuronal activity in deep brain tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If surgical implants are used for optogenetic stimulation, then optogenetic modulation can be achieved, but tissue damage and susceptibility to infection increase
Solution Approach 1:
The patent extracts and removes the surgical implant component from the optogenetic system. By using externally deliverable optogenetic compositions (viral vectors, AAVs, LENTIVIRUSES) that can be administered systemically or locally without surgical implantation, the harmful effects of implants are eliminated while maintaining optogenetic modulation capability through non-invasive delivery methods
Solution Approach 2:
The patent introduces intermediary substances (optogenetic compositions, viral vectors, photosensitive proteins like channelrhodopsin and halorhodopsin) that mediate the optogenetic effect without requiring direct surgical implantation. These intermediaries can be delivered through blood-brain barrier penetration or local injection, serving as a bridge between external light sources and target neurons without mechanical implants
2Reliability
If traditional optogenetic methods are used, then neuronal activity can be modulated, but anatomical coverage is limited due to light attenuation in deep brain tissues
Solution Approach 1:
The patent changes the optical parameters by using red-shifted optogenetic tools (halorhodopsin activated by orange light, channelrhodopsin-2 activated by blue light) that have deeper tissue penetration capabilities compared to traditional green-light activated opsins. This parameter change in wavelength and activation threshold enables effective modulation of deep brain structures with reduced light attenuation
Solution Approach 2:
The patent employs prolonged activation kinetics of step-function opsins where brief light pulses trigger sustained neuronal activation or inhibition lasting minutes to hours. This periodic action with extended duration compensates for light attenuation by achieving deep tissue coverage through temporal integration rather than relying solely on high light intensity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
SOUL enables reversible and prolonged activation of neurons at significant depths within the brain, disrupting behaviors like feeding in mice and modulating spiking activity in macaques, providing a minimally invasive approach to optogenetic manipulation with increased anatomical coverage and reduced tissue damage.
Implementation Method 1
a step-function opsin (SFO) polypeptide that includes at least two stabilized step function mutations and at least one peak amplitude increasing mutation
Data Source
AI summary
The present disclosure provides compositions and methods for minimally invasive optogenetic stimulation. More particularly, the present disclosure provides compositions and methods for using an ultra-sensitive step-function opsin for minimally invasive optogenetic stimulation.